Ethanol → Ethyl 4-chloropyridine-3-carboxylate

Temperature

80 °C

A suspension of 4-chloro-pyridine-3-carboxylic acid (5.0 g, 31.7 mmol) in thionyl chloride (100 ml) is heated at 80° C. for 1.5 h. The reaction mixture is cooled to RT and excess thionyl chloride is distilled off. The crude product is azeotropped with toluene (3×30 ml) to afford a solid, which is added in portions to a mixture of ethanol (40 ml) and diisopropylethylamine (25 ml) at 0° C. The resulting reaction mixture is stirred at RT for 4 h. After completion of the reaction, the mixture is evaporated to dryness; the residue is diluted with water (20 ml) and extracted with EtOAc (3×25 ml). The combined organic layers are washed with water (30 ml), brine (30 ml), dried over anhydrous sodium sulfate and evaporated to get 4-chloro-pyridine-3-carboxylic acid ethyl ester (4.50 g, 24.3 mmol, 77%), which is used in the next step without further purification.

1. temperatureThe reaction mixture is cooled to RT
2. distillationexcess thionyl chloride is distilled off
3. customto afford a solid, which
4. customThe resulting reaction mixture
5. customAfter completion of the reaction
6. customthe mixture is evaporated to dryness
7. additionthe residue is diluted with water (20 ml)
8. extractionextracted with EtOAc (3×25 ml)
9. washThe combined organic layers are washed with water (30 ml), brine (30 ml)
10. dry with materialdried over anhydrous sodium sulfate
11. customevaporated

ORD record

ord-54a1254efb6842b5afecbff0e3d6209b

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09284286B2